a study comparing two doses of agtc-501 in male subjects with x-linked retinitis pigmentosa caused by rpgr mutations (skyline)

Conditions: X-Linked Retinitis Pigmentosa

Summary: this study will evaluate the safety and efficacy of a recombinant adeno-associated virus vector (raav2tyf-grk1-rpgr) in patients with x-linked retinitis pigmentosa caused by rpgr mutations.

approximately 12 participants, who were not part of the phase 1/2 (horizon) study, will be enrolled into the dose expansion portion of the study. these participants will be randomized in a 1:1 ratio to 1 of 2 treatment groups (i.e., group 1 \[low dose\] and group 2 \[high dose\]). each participant will receive the assigned dose of agtc-501 in one eye on a single occasion.

Eligibility criteria:
inclusion criteria: * provide written informed consent or assent (per local regulation), prior to the conduct of any study-related procedure. subjects who provide assent must have a parent, guardian, or legal representative provide written informed consent. * be between 8 and 50 years of age (inclusive) at the time of informed consent and assent (as applicable). * be male and have at least one documented pathogenic or likely pathogenic variant in the rpgr gene * have a clinical diagnosis of xlrp. * have a bcva no better than 75 letters and no worse than 35 letters based on an etdrs chart at each screening visit. * be able to perform all tests of visual and retinal function and structure in both eyes based on the subject's reliability, and fixation, per the investigator's discretion. * have detectable baseline mean macular sensitivity measured by (maia) microperimetry, as determined by the investigator and confirmed by the central reading center (crc). * have detectable ez line in both eyes as assessed by sd-oct and confirmed by the crc. exclusion criteria: * have other known disease-causing mutations documented in the subject's medical history or identified through a retinal dystrophy gene panel, that in the opinion of the investigator would interfere with the potential therapeutic effect of the study agent or the quality of the assessments. * for subjects with herpes simplex virus (hsv): 1. have history of oral or genital herpes and unable and/or unwilling to utilize prophylactic antiviral medication. 2. have a history of ocular herpes. 3. have active oral or genital herpes or are currently receiving treatment for hsv infection. * have complicating systemic diseases (e.g., medical conditions causing immunosuppression, active systemic infection) that would preclude the gene transfer or ocular surgery. * have known sensitivity or allergy to systemic corticosteroids or other immunosuppressive medications. * have used anti-coagulant agents that may alter coagulation * have received any vaccination/immunization within 28 days prior to screening and/or during screening with the exception of the influenza vaccine, which is only exclusionary if they have received the influenza vaccine within 28 days prior to randomization. * have used systemic corticosteroids or other immunosuppressive medications within 3 months prior to screening and/or intend to use during screening. * have previously received any aav gene therapy product, stem cell therapy, cell-based therapy, or similar biologics. ocular exclusion criteria (either eye): * have pre-existing eye conditions that would preclude the planned surgery, interfere with the interpretation of study endpoints, or increase the risk of surgical complications * have significant media opacity impacting evaluation of the retina or vitreous. * had intraocular surgery within 90 days of study treatment administration. * have any active ocular/intraocular infection or inflammation * have a history of steroid-induced raised iop of \>25 mmhg following corticosteroid exposure, despite topical iop-lowering pharmacologic therapy. * have any artificial retinal implant or prosthesis. * have absence of clear ocular media and/or inadequate pupil dilation to facilitate good quality oct images. * have any history of rhegmatogenous retinal detachment. * have myopia (spherical equivalent) exceeding -10 diopters (or axial length of \>30 mm if pi deems it appropriate to measure) or presence of pathologic myopia in the study eye. * have passed the low contrast ora-vnc™ mobility course in either eye or binocularly at any screening visit.

Keywords: xlrp retinal degeneration rpgr adeno-associated virus gene therapy aav